Abstract
Cancer vaccines, which activate the immune system against a target antigen, are attractive for prostate cancer, where multiple upregulated protein targets are identified. However, many clinical trials implementing peptides targeting these proteins have yielded suboptimal results. Using spherical nucleic acids (SNAs), we explore how precise architectural control of vaccine components can activate a robust antigen-specific immune response in comparison to clinical formulations of the same targets. The SNA vaccines incorporate peptides for human prostate-specific membrane antigen (PSMA) or T-cell receptor γ alternate reading frame protein (TARP) into an optimized architecture, resulting in high rates of immune activation and cytolytic ability in humanized mice and human peripheral blood mononuclear cells (hPBMCs). Specifically, administered SNAs elevate the production and secretion of cytokines and increase polyfunctional cytotoxic T cells and effector memory. Importantly, T cells raised from immunized mice potently kill targets, including clinically relevant cells expressing the whole PSMA protein. Treatment of hPBMCs increases costimulatory markers and cytolytically active T cells. This work demonstrates the importance of vaccine structure and its ability to reformulate and elevate clinical targets. Moreover, it encourages the field to reinvestigate ineffective peptide targets and repackage them into optimally structured vaccines to harness antigen potency and enhance clinical outcomes.
| Original language | English (US) |
|---|---|
| Article number | 2101262 |
| Journal | Advanced Healthcare Materials |
| Volume | 10 |
| Issue number | 22 |
| DOIs | |
| State | Published - Nov 17 2021 |
Funding
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award No. U54CA199091. The content was solely the responsibility of the authors and did not necessarily represent the official views of the National Institutes of Health. This project was also supported by the Prostate Cancer Foundation and the Movember Foundation under Award No. 17CHAL08, the Convergence Science Medicine Institute seed award, and the Polsky Urologic Cancer Institute of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University at Northwestern Memorial Hospital. M.H.T. acknowledges support from Northwestern University's Cancer Nanotechnology Training Program Award No. T32CA186897. J.W.D. and S.W. acknowledge support from the Chemistry of Life Processes Predoctoral Training Program at Northwestern University. M.E. was partially supported by the Dr. John N. Nicholson Fellowship. The content was solely the responsibility of the authors and did not necessarily represent the official views of Northwestern University. Peptide synthesis was performed at the Peptide Synthesis Core Facility of the Simpson Querrey Institute at Northwestern University, with special thanks to Dr. Mark Karver, which has current support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (Grant No. NSF ECCS-2025633). This work made use of the IMSERC MS facility at Northwestern University, with special thanks to Mr. Saman Shafaie, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (Grant No. NSF ECCS-2025633), the State of Illinois, and the International Institute for Nanotechnology (IIN). The authors thank Dr. Timothy Kuzel for the PC3-PSMA cells. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award No. U54CA199091. The content was solely the responsibility of the authors and did not necessarily represent the official views of the National Institutes of Health. This project was also supported by the Prostate Cancer Foundation and the Movember Foundation under Award No. 17CHAL08, the Convergence Science Medicine Institute seed award, and the Polsky Urologic Cancer Institute of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University at Northwestern Memorial Hospital. M.H.T. acknowledges support from Northwestern University's Cancer Nanotechnology Training Program Award No. T32CA186897. J.W.D. and S.W. acknowledge support from the Chemistry of Life Processes Predoctoral Training Program at Northwestern University. M.E. was partially supported by the Dr. John N. Nicholson Fellowship. The content was solely the responsibility of the authors and did not necessarily represent the official views of Northwestern University. Peptide synthesis was performed at the Peptide Synthesis Core Facility of the Simpson Querrey Institute at Northwestern University, with special thanks to Dr. Mark Karver, which has current support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (Grant No. NSF ECCS‐2025633). This work made use of the IMSERC MS facility at Northwestern University, with special thanks to Mr. Saman Shafaie, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (Grant No. NSF ECCS‐2025633), the State of Illinois, and the International Institute for Nanotechnology (IIN). The authors thank Dr. Timothy Kuzel for the PC3‐PSMA cells.
Keywords
- humanized mice models
- nanotechnology
- prostate cancer
- spherical nucleic acids (SNAs)
- vaccine immunotherapy
ASJC Scopus subject areas
- Biomaterials
- Biomedical Engineering
- Pharmaceutical Science
